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Abstract：
CD4 T cell activation induces nuclear and cytoplasmic actin polymerization via the Arp2/3 complex to activate cytokine expression and strengthen T cell receptor (TCR) signaling. Actin polymerization dynamics and filament morphology differ between nucleus and cytoplasm. However, it is unclear how the Arp2/3 complex mediates distinct nuclear and cytoplasmic actin polymerization in response to a common stimulus. In humans, the ARP3, ARPC1, and ARPC5 subunits of the Arp2/3 complex exist as two different isoforms, resulting in complexes with different properties. Here, we show that the Arp2/3 subunit isoforms ARPC5 and ARPC5L play a central role in coordinating distinct actin polymerization events in CD4 T cells. While ARPC5L is heterogeneously expressed in individual CD4 T cells, it specifically drives nuclear actin polymerization upon T cell activation. In contrast, ARPC5 is evenly expressed in CD4 T cell populations and is required for cytoplasmic actin dynamics. Interestingly, nuclear actin polymerization triggered by a different stimulus, DNA replication stress, specifically requires ARPC5 but not ARPC5L. TCR signaling but not DNA replication stress induces nuclear actin polymerization via nuclear calcium-calmodulin signaling and N-WASP. Diversity in the molecular properties and individual expression patterns of ARPC5 subunit isoforms thus tailors Arp2/3-mediated actin polymerization to different physiological stimuli.
摘要：
CD4T细胞活化通过Arp2/3复合物诱导细胞核和细胞质肌动蛋白聚合，以激活细胞因子表达并增强T细胞受体（TCR）信号传导。细胞核和细胞质之间的肌动蛋白聚合动力学和细丝形态不同。然而,目前尚不清楚Arp2/3复合物如何介导不同的核和细胞质肌动蛋白聚合以响应共同的刺激。在人类中,Arp2/3复合物的ARP3、ARPC1和ARPC5亚基以两种不同的亚型存在，导致具有不同性质的复合物。这里,我们表明，Arp2/3亚基同工型ARPC5和ARPC5L在协调CD4T细胞中不同的肌动蛋白聚合事件中起着核心作用。虽然ARPC5L在单个CD4T细胞中异质表达，它在T细胞激活时特异性驱动核肌动蛋白聚合。相比之下,ARPC5在CD4T细胞群中均匀表达，是细胞质肌动蛋白动力学所必需的。有趣的是,由不同的刺激引发的核肌动蛋白聚合，DNA复制应激,特别需要ARPC5而不是ARPC5L。TCR信号而不是DNA复制应激通过核钙-钙调蛋白信号和N-WASP诱导核肌动蛋白聚合。因此，ARPC5亚基同工型的分子特性和个体表达模式的多样性使Arp2/3介导的肌动蛋白聚合适应不同的生理刺激。
